Matteo Cornaggia

Three subtypes of gastric argyrophil carcinoid and the gastric neuroendocrine carcinoma: A clinicopathologic study

BACKGROUND Enterochromaffinlike (ECL) cell carcinoids recently observed in rats stimulated new interest in gastric endocrine tumors arising in humans. METHODS Paraffin-embedded sections of 55 endocrine tumor cases were stained with H&E, mucin tests were performed, and immunoperoxidase was used for detecting endocrine markers; 23 cases were also investigated ultrastructurally. RESULTS Forty-five argyrophil carcinoids, 9 neuroendocrine carcinomas, and 1 gastrinoma were identified. Three clinicopathologic subtypes of carcinoids were characterized: (1) twenty-eight cases, none metastatic, arose in a background of body-fundus atrophic gastritis and hypergastrinemia; (2) seven cases, 2 locally metastatic, were associated with hypertrophic gastropathy and hypergastrinemia due to multiple endocrine neoplasia/Zollinger-Ellison syndrome; and (3) ten were sporadic cases, 7 of which were deeply invasive, 6 metastatic, and 5 histologically atypical. All carcinoids showed histochemical and ultrastructural patterns of ECL cells. The 9 neuroendocrine carcinomas, all deeply invasive and metastatic, were composed of anaplastic, small- to intermediate-sized cells with high mitotic index and focal necrosis. CONCLUSIONS Gastrin-promoted carcinoids represent a benign or low grade tumor disease, whereas sporadic carcinoids and neuroendocrine carcinomas are life-threatening neoplasms, independent of gastrin promotion.

Gastric Carcinoids and Related Endocrine Growths

A series of 30 gastric endocrine tumours has been revised in the light of available available cytologic and clinicopathologic information. Among 24 well differentiated endocrine tumours-16 with and 8 without chronic atrophic gastritis (CAG)-3 gastrin cell tumours have been distinguished from 21 argyrophil carcinoids, 15 of which showed light- and/or electronmicroscopy patterns of enterochromaffin-like (ECL) cell tumours, 2 of EC cell tumours and 1 of D1/P cell tumour. One case of mixed carcinoid/adenocarcinoma and 5 cases of endocrine carcinomas, 4 poorly and 1 moderately differentiated, were also identified. Achlorhydria, due to type A CAG or HCl-suppressing drugs, and bombesin hyperstimulation are among possible factors inducing G cell hyperfunction and/or hyperplasia. Hypergastrinaemia is among causative agents of argyrophil ECL cell hyperplasias and, possibly, of tumours of the oxynticopeptic mucosa, while chronic inflammation and gland atrophy with or without concomitant hypergastrinaemia are important factors in inducing both hyperplastic and tumour argyrophil growths in CAG mucosa.

Cathepsin E in follicle associated epithelium of intestine and tonsils: localization to M cells and possible role in antigen processing

A specific rabbit anti-human serum was used selectively to localize the aspartic proteinase cathepsin E to follicle associated epithelium (FAE) of human and rat intestine, including jejunum, ileum, appendix, colon and rectum, as well as of human palatine, pharyngeal and lingual tonsils. Coexpression of class II histocompatibility antigen HLA-DR antigen has been observed in some of the cathepsin E-positive epithelial cells. In addition, cathepsin E has been detected in a few mononuclear cells of intestinal lymphoid structures and tonsils resembling interdigitating reticulum cells of lymph nodes. Another aspartic proteinase, cathepsin D, has been found to be poorly represented in FAE and intensely expressed by macrophages. Electron immunocytochemistry localized cathepsin E to endosomal vesicles and endoplasmic reticulum of M cells in rat and human ileum as well as of M-like cells in human palatine tonsil. The results suggest a possible role of endosomal cathepsin E in the processing of macromolecules and microorganisms transported by M cells and related epithelial cells to mucosal associated lymphoid tissue (MALT).

Session 5: Morphology and Pathogenesis of Endocrine Hyperplasias, Precarcinoid Lesions, and Carcinoids Arising in Chronic Atrophic Gastritis

Solcia E, Fiocca R, Villani L, Gianatti A, Cornaggia M, Chiaravalli A, Curzio M, Capella C. Morphology and pathogenesis of endocrine hyperplasias, precarcinoid lesions, and carcinoids arising in chronic atrophic gastritis. Scand J Gastroenterol 1991, 26(suppl 180), 146–159The spectrum of endocrine cell changes occurring in 80 cases of body-fundus chronic atrophic gastritis (CAG), mostly type A or multifocal, including various types of hyperplasia, precarcinoid lesions (20 cases), and neoplasia (carcinoid, 24 cases) have been analyzed histologically, histochemically, and ultrastructurally. Changes associated with gland atrophy, pyloric- or intestinal-type metaplasia, regenerative hyperplasia, and hypergastrinemia have been identified and their neoplastic potential evaluated in the light of their proliferative capacity (bromodeoxyuridine incorporation) and clinicopathologic behavior. A close link between disseminated precarcinoid lesions of non-tumor mucosa and multiple carcinoids (carcinoidosis) arising in...

Characterization of Four Main Cell Types in Gastric Cancer: Foveolar, Mucopeptic, intestinal Columnar And Goblet Cells: An histopathologic, histochemical and ultrastructural study of “early” and “advanced” tumours

Gastrectomy specimens of 148 gastric cancers, 40 of them being intramucosal or microinvasive, 27 penetrating the submucosa and 81 invading the muscularis propria, with or without involvement of the serosa and perigastric tissues, have been investigated with conventional histopathologic techniques, mucin histochemistry and electron microscopy to characterize the various lines of tumour cell differentiation and to correlate these with the histologic patterns of tumour growth. More or less differentiated intestinal columnar, intestinal goblet, gastric foveolar or mucopeptic cells were recognized in most tumours, of glandular, diffuse or mucoid type. Although simultaneous expression of more than one cell type into the same tumour occurred very frequently, intestinal columnar cells were more prominent in tubular adenocarcinomas, goblet cells (especially of colorectal type) in mucoid cancers, mucopeptic cells in diffuse cancers of invasive desmoplastic type and foveolar cells in diffuse cancers of intramucosal signet-ring cell type. In general, an increased tendency to foveolar cell differentiation and a reduced tendency to mucopeptic differentiation has been found in intramucosal cancers as compared to invasive cancers. It is concluded that the type of tumour cell differentiation, which might have some influence on the natural history of gastric cancer, is better related with more defined tumour subtypes than with the usually recognized glandular or diffuse patterns.

Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia

Abstract Immunohistological analysis of the expression of lactase protein in adults with hypolactasia has been carried out using monoclonal antibodies. Eight different antibodies that recognize at least three distinct epitopes on the lactase protein each gave the same result. Strong brush border staining was observed in all the lactase-persistent adults. No staining at all was detected in 9 of the hypolactasic subjects. In the remaining 12 individuals a mosaic pattern of expression was observed: small patches of enterocytes stained strongly, whereas the surrounding areas showed no staining at all. Sucraseisomaltase, in contrast, showed no such mosaicism in these or in any of the other individuals. The mosaicism observed in the 12 hypolactasic individuals suggests that the differentiation of the columnar cells along the villus is not homogeneous. Furthermore, the existence of two patterns of expression of the lactase protein in the lactase-deficient individuals (i.e., absence of protein and mosaicism), if characteristic of the entire length of the intestine of the individuals tested, would suggest the existence of two phenotypes of adult-type hypolactasia in the population studied.

Histopathology, Cytology and Cytochemistry of Pheochromocytomas and Paragangliomas Including Chemodectomas

The results of histopathological, histochemical and ultrastructural investigations on pheochromocytomas and paragangliomas have been reported. These results allowed the functional identification of the cell types composing many of such tumours. Moreover, comparison of these data with clinico-pathologic findings outlined the advantages and limits of cytologic studies for understanding the natural history of pheochromocytomas and paragangliomas and improving our diagnostic and prognostic criteria.

Electron immunocytochemical localization of pepsinogen I (PgI) in chief cells, mucous-neck cells and transitional mucous-neck/chief cells, of the human fundic mucosa

SummarySpecific PgI antibodies devoid of PgII cross reactivity have been applied to aldehyde-osmium fixed human, fundic-type, gastric mucosa investigated with the protein A-immunogold technique. PgI immunoreactivity has been detected in the homogeneous secretory granules of glandular chief cells, in bipartite granules of mucous-neck cells, in the granules of cells showing intermediate patterns and topography in between chief and mucous-neck cells (transitional cells), as well as in the granules of a few cells in the foveolar/mucous-neck boundary zone showing mixed foveolar/mucous-neck granule populations. The findings support progressive transformation of mucous-neck cells into chief cells.

Ultrastructural localization of motilin in endocrine cells of human and dog intestine by the immunogold technique

SummaryMotilin-immunoreactivity has been localized by two electron immunocytochemical techniques, using goldlabelled protein A or IgG as second layer, in a specific type of endocrine cell scattered in the epithelium of human and canine upper small intestine. The motilin (M) cell is characterized by relatively small (180 nm in man; 200 nm in the dog), solid granules with homogeneous core and closely applied membrane, round in man, round to irregularly-shaped in the dog. Perinuclear microfilaments are prominent in human motilin cells.

Expression of pepsinogen II in gastric cancer. Its relationship to local invasion and lymph node metastases

We have determined the prevalence of pepsinogen II (PG II) immunoreactive cells in a large series of early and advanced gastric cancers and relationships among PG II‐positivity, tumor histologic type, extent of gastric wall invasion, and presence of lymph node metastases. Of the 316 cancers evaluated, 150 (47%) expressed PG II. The prevalence by histologic type was 55% in 146 glandular tumors, 43% in 83 diffuse tumors, 16% in 25 mucoid tumors, and 51% in 59 mixed‐type cancers. Two parietal cell cancers and one undifferentiated cancer were PG II‐negative. In glandular and diffuse cancers, but not mucoid and mixed tumors, both the extent of gastric wall invasion and incidence of lymph node metastases were associated positively with PG II expression by the primary tumor. In particular, PG II‐reactive cells were found significantly more often in advanced than in early diffuse cancers (P < 0.05) and significantly more often in submucosal early cancers than in intramucosal early cancers (P < 0.01). The prevalence of PG II expression also was higher significantly in metastatic cancers than in nonmetastatic cancers. This was true for advanced gastric cancers as a whole (P < 0.01), advanced glandular‐type cancer alone (P < 0.01), advanced glandular‐ and diffuse‐ type cancers together (P < 0.001), and early diffuse‐type cancer (P < 0.05). Only four (3%) of 145 cancers evaluated for pepsinogen I (PG I) were positive, and each also was positive for PG II. The results suggest that the expression of PG II by glandular and diffuse types of gastric cancer may be a marker of increased malignancy.